Semaglutide treatment for obesity in teenagers: a plain language summary of the STEP TEENS research study

Plain language summary What is this summary about? This is a plain language summary of the STEP TEENS research study, which was originally published in the New England Journal of Medicine. As more teenagers are living with obesity than ever before, researchers are searching for new treatments. This was the first study looking at how well the medicine semaglutide works as a treatment for obesity in teenagers. What were the results? In this study, researchers looked at the effect of semaglutide on body mass index (BMI) and weight loss compared to a dummy medicine (placebo). A 17% decrease in BMI was reported for teenagers treated with semaglutide compared with placebo. For weight loss, an 18 kg decrease was seen when comparing semaglutide with placebo. Researchers found that there were more teenagers who had weight loss of 5%, 10%, 15%, and 20% or more in the group given semaglutide compared with the group given placebo. Improvements were also seen with semaglutide treatment for some risk factors for other diseases caused by obesity. Semaglutide was generally well tolerated by the teenagers with obesity in this study, and serious medication side effects did not happen very often. What do the results mean? The results from this study showed that there were no safety issues with semaglutide in teenagers with obesity, and that semaglutide can be used to help them lose weight. Clinical Trial Registration: NCT04102189 (ClinicalTrials.gov)


Diabetes
High blood pressure

Blood lipid problems
Liver disease Sleep problems

Mental health issues
Poor quality of life Social issues (e.g., bullying)

Body weight
As obesity is a long-term or chronic disease, teenagers who have it will need ongoing support from caregivers and healthcare professionals to help them achieve and maintain weight loss.
Body Mass Index (which is also known as BMI) is the most common method used by healthcare professionals to check for obesity. It uses your weight and height to calculate if your weight is healthy. As you grow, your BMI changes. For children and teenagers, a normal BMI for their age can be found using growth charts (examples for girls and boys based on the charts developed by the USA Centers for Disease Control and Prevention are shown below). Based on these charts, a child or teenager is considered to have obesity if their BMI is in the 95 th percentile or higher for their age and sex. If their BMI falls between the 85 th and 95 th percentile they are classed as overweight. 10.2217/cer-2022-0187 Semaglutide treatment for obesity in teenagers: STEP TEENS reasearch study Plain Language Summary of Publication  Lifestyle changes, like eating healthily and exercising every day, are usually the first steps to treat obesity in teenagers. However, most people find it hard to lose weight and keep it off with lifestyle changes alone because the body will try hard to resist these efforts.
Medicines can be added to lifestyle changes to help with weight loss. Some medicines can make people feel less hungry and fuller after eating meals, and/or reduce cravings for certain types of unhealthy foods. Other medicines can stop the body from absorbing fat from meals. At the moment, there are not many medicines available for teenagers who have obesity.

What is semaglutide?
Semaglutide is a medicine that helps adults with obesity to lose weight. It is also used to treat type 2 diabetes, a disease that happens when you have too much sugar in your blood, which can be caused by excess weight gain or obesity.
Semaglutide is similar to a hormone called glucagon-like peptide-1 (also known as GLP-1), which is made in the body. GLP-1 helps control the amount of sugar (glucose) in your blood and makes you feel less hungry and fuller after eating.

What did researchers want to find out?
More teenagers are living with obesity than ever before, and the numbers continue to rise. Researchers are searching for new medicines to help these teenagers lose weight.
The STEP TEENS research study looked at whether semaglutide could be a possible treatment for obesity in teenagers.

million
children and teenagers worldwide will have obesity by 2030 It is predicted that more than How was the STEP TEENS study carried out?
The STEP TEENS study included four parts: 1. Screening: During screening, teenagers who wanted to take part in the study were checked to make sure they met the entry requirements, for example, that they were the right age and had a high enough BMI. The teenagers who met all requirements moved on to the run-in period.

Run-in period:
During the run-in, the teenagers and their caregivers were given advice on how to eat healthily and exercise more. The teenagers were asked to exercise and eat healthily for 12 weeks to see if they could lose weight with these activities alone. The teenagers who completed the run-in period but still had a high enough BMI started treatment.
3. Treatment period: During treatment, the teenagers were randomized and split into two groups. One group was given placebo once per week and the other group was given semaglutide once per week for a total of 68 weeks. The treatments in this study were given as an injection under the skin. Semaglutide was started with a low dose, which was slowly increased to higher doses over time. Semaglutide doses were increased until the maintenance dose (2.4 mg) was reached. The amount of placebo given was also increased so that the same amount as the semaglutide treatment was given, even though there was no active medicine in the placebo. As the teenagers were put in each group by chance (i.e., randomized), they and their caregivers did not know which treatment they were given. While they had treatment, the teenagers and their caregivers continued to be given advice on healthy eating and exercise. After 68 weeks, treatment was stopped, and the follow-up period started.

Follow-up period:
During follow-up, each teenager was monitored for another 7 weeks to make sure they were okay after treatment.
Plain Language Summary of Publication Weghuber, Boberg, Hesse and co-authors In total, the STEP TEENS study was 75 weeks long and included a total of 201 teenagers. For every three teenagers who took part, two were randomly assigned to treatment with semaglutide, and one was randomly assigned to treatment with placebo.
To see which teenagers could take part in the study To see if teenagers taking part in the study lost weight with lifestyle changes such as changes in diet and exercise Teenagers were randomly selected and given semaglutide or placebo once per week by injection under the skin.
The dose of semaglutide was increased slowly over 16 weeks to 2.4 mg Teenagers were monitored for safety Aged 12 or over, but less than 18 years old Boys and girls with a BMI well above the normal range (≥95 th percentile) compared with other boys and girls of the same age and sex Boys and girls with a BMI slightly above the normal range (≥85 th percentile) could also take part if they had weight-related health problems Not able to lose weight with diet and exercise Being treated with diet and exercise if they also had diabetes. They could also be using a diabetes medicine called metformin.
People who could not take part in the study were those: Whose weight had increased or decreased by 5 kg (11 lbs) or more in the past 3 months Who had taken another medicine to treat their obesity in the past 3 months Who had had surgery to treat their obesity With other diseases such as thyroid problems, severe depression, severe mental health disorders, eating disorders, or attempts at suicide.
The age and proportion of boys and girls in the semaglutide and placebo treatment groups were similar, but body weight, BMI, and waist circumference were slightly higher in the semaglutide group at the start of the study.

Who took part in the study?
This was a global study and included participants from 37 study sites in 8 countries. Other: 9%

Placebo group
The STEP TEENS study took place between October 2019 and March 2022.
The study compared BMI between teenagers who were given semaglutide and teenagers who were given placebo. Both treatments were given for 68 weeks.
The study went as planned. Almost all of the teenagers (90%) completed their treatment. All of the teenagers started on a low dose and increased to a maintenance dose. For those who could not tolerate the maintenance dose, lower doses were used instead to continue treatment.

BMI and body weight decreased in teenagers who were given semaglutide
After 68 weeks of treatment, the researchers measured the BMI of each teenager.

1%
The treatment difference for BMI between semaglutide and placebo was therefore reported to be around -17%.

Change in BMI (%) during the study Participant details
10.2217/cer-2022-0187 Semaglutide treatment for obesity in teenagers: STEP TEENS reasearch study Plain Language Summary of Publication As well as BMI, the researchers wanted to see how the teenagers' weight had changed after treatment.
They found that: Teenagers The treatment difference for weight between the semaglutide and placebo groups was around -18 kg (40 lb).

More teenagers in the semaglutide group achieved a beneficial level of BMI reduction compared with the placebo group
The researchers also looked at how many teenagers in each treatment group had a decrease in their BMI of 5% or more since the start of the treatment period. This level of BMI reduction is known to improve health. Many more teenagers in the semaglutide group had reached this level of decrease in their BMI compared with the placebo group. The number of participants here might be different from the number of participants who started the study. This is because these numbers only include the participants who had a BMI measurement at both the start and the end of the study.

Change in weight (kg) during the study 3 More teenagers in the semaglutide group reached different levels of weight loss than in the placebo group
They also considered how many teenagers in each treatment group had different levels of weight loss since the start of the study (5% or more, 10% or more, 15% or more, and 20% or more). Many more teenagers in the semaglutide group reached each level of weight loss than in the placebo group.

Teenagers with weight loss
The number of participants here might be different from the number of participants who started the study. This is because these numbers only include the participants who had a body weight measurement at both the start and the end of the study.

Teenagers who were given semaglutide reported better results in other weight-related risk factors than teenagers given placebo
Researchers also looked at other risk factors that are related to diseases caused by obesity to see how they were affected by semaglutide.
Compared with placebo, semaglutide: • Reduced the size of the teenagers' waists • Reduced the levels of sugar in the teenagers' blood in those with and without diabetes • Improved the levels of some types of lipids (fats) in the teenagers' blood • Improved the results of a test that shows how well the liver is working.
The teenagers who were given semaglutide also reported better scores than those given placebo on a questionnaire about how their weight affects their lives and how they feel about themselves. 1 There were no safety issues with semaglutide in teenagers with obesity This study suggests that there were no safety issues with semaglutide in teenagers with obesity.
The number of teenagers reporting side effects with semaglutide was similar to the number reporting side effects with placebo. The most common serious side effect was gallstones, which did not happen very often. No deaths were reported in this study.

%
The number of participants here might be different from the number of participants who started the study. This is because these numbers only include the participants who received a dose of study treatment.

Semaglutide
Semaglutide treatment for obesity in teenagers: STEP TEENS reasearch study Plain Language Summary of Publication 2 The most common side effects with semaglutide were stomach problems The most common side effects with semaglutide were stomach problems, such as nausea and vomiting (feeling sick or being sick to the stomach). These side effects were expected by the researchers, as similar side effects have also been seen in other studies with semaglutide and in studies of other similar medicines. Most of the side effects were mild and happened at the beginning of the study while the teenagers got used to the medicine. For most of the teenagers, these side effects went away after a few weeks.

Glossary of terms used in this summary
Plain Language Summary of Publication Weghuber, Boberg, Hesse and co-authors

What do the results of this study mean?
This study is the first to find out whether semaglutide can be used to treat obesity in teenagers aged 12 or over, but less than 18 years old.
In this study, researchers looked at the effect of the medicine semaglutide on BMI compared with placebo.
The researchers reported benefits in teenagers treated with semaglutide compared with placebo. These included: • A decrease in BMI of around 17% • Weight loss of around 18 kg (40 lbs) • More teenagers achieving weight losses of more than 5%, 10%, 15%, and 20% compared with the group given placebo • Improvements in some risk factors for other diseases caused by obesity.
Semaglutide is already used to treat overweight (with underlying health issues) and obesity (with or without underlying health issues) in adults. The side effects reported for semaglutide in this study in teenagers were similar to the side effects of semaglutide in adults.
The results from this study show that semaglutide can be used to help teenagers with obesity to lose weight when it is used alongside healthy eating and exercise. These results are for this study only. Other studies with different types of people may show different results.
Blinding: When people take part in a research study and they do not know which of the medicines being studied are being given to them, it is called "blinding". For research studies that use a placebo (a dummy medicine that has no effect on the body; see Placebo) in a blinded fashion, the people taking part do not know if they are given the placebo or the active medicine. This is because knowing you are taking a placebo can change how you behave in a study, which can in turn affect the results. This way researchers can see if the active medicine works as it was expected to.
Blood lipids: Your blood is the transport system used by your body to carry many things essential for life. These include red blood cells that carry oxygen and white blood cells that help the body fight off infections. Particles of fat are also present in the blood, which the body can use as energy. However, because fat does not dissolve in water, fats have to be carried around the body in special packages called lipids. Lipids can join with proteins in your blood to form lipoproteins, which are important to the cells in the body and are used for making energy. If the levels of lipids in the blood are too high, it can lead to problems with your heart and blood vessels.
Blood pressure: The pressure of the blood circulating in your body pushes against the walls of your veins and arteries. Most of the pressure comes from the heart pumping blood through the blood vessels.
Blood sugar: The level of sugar (called glucose) in the blood.

Body mass index:
Often shortened to BMI. A measurement used to find out if you are a healthy weight for your height. A healthy BMI in children and teenagers depends on their age and sex. This is because their height, weight, and body fat are affected by growth and development. Most children and teenagers are considered a healthy weight if their BMI is above the 5 th percentile and below the 85 th percentile of a reference (i.e., similar) population of other people of the same age and sex (see Percentile).